The Case of the Killer Vitamins Revisited

A lot of people have asked about the Atlantic article by Paul Offit, “The Vitamin Myth: Why We Think We Need Supplements.” Offit, a pediatrician, is best known for his defense of childhood immunizations. In arguing against benefits from vitamins, as he did in arguing against harm from vaccines, he takes a strong stand.

Before I take a look at his article, let me mention a competing publication about supplements that became available today, and might be more worthy of your time.

Examine.com’s Supplement Goals Reference Guide

A friend of the blog, Sol Orwell, has been an expert on nutritional supplements for many years and has consulted extensively for vitamin and supplement manufacturers. He and his colleagues have spent years compiling the most extensive database of peer-reviewed literature available, and have compiled the data into a 762 page reference guide that has a comprehensive overview of the supplement literature. It is an encyclopedic resource with background information about almost every supplement that has been studied, including herbal remedies, each graded for quality of evidence, and easily searchable by:

supplement, to view the evidence for effects, good and bad, of each supplement; and

The Atlantic Article

OK, so what evidence does Offit compile against supplements?

Central to his case is a paper that we’ve already discussed on this blog (“Around the Web; The Case of the Killer Vitamins,” October 15, 2011): the 2011 analysis of the Iowa Women’s Health Study by Jaakko Mursu and collaborators in Archives of Internal Medicine. [1] Offit highlights it in the very first sentence of his article:

On October 10, 2011, researchers from the University of Minnesota found that women who took supplemental multivitamins died at rates higher than those who didn’t.

Apart from this reference he discusses two issues:

Linus Pauling’s argument that vitamin C can prevent colds and cancer has not been supported. A history of Pauling’s romance with vitamin C occupies about two-thirds of the article, and Offit seems to think the whole idea of supplementation was originated by Pauling and persists due to his influence (“What few people realize, however, is that their fascination with vitamins can be traced back to one man,” Pauling.).

Multiple studies have shown that supplementing vitamins A and E is often harmful.

This is hardly a comprehensive case against supplementation; it only shows that a few supplements tend to be harmful or lack benefits.

Regarding vitamins A and E, we agree; they are noted in our book as nutrients that should generally not be supplemented, or should be supplemented in low doses from natural sources. For example, we recommend eating a quarter pound of liver per week for vitamin A and other nutrients.

Regarding vitamin C, that it may not prevent colds or cancer does not mean it has no benefits. A few:

Our book has more evidence for benefits of vitamin C supplementation. Many people notice improved skin, hair, nails, gums, and teeth when supplementing with vitamin C, and faster wound healing. Vitamin C needs rise dramatically in sickness and stress.

It would be easy enough to compile further evidence of benefits of supplementation. Indeed, it was not so long ago that pellagra was rampant in the US South, and beriberi in East Asia. Many foods are subject to mandatory micronutrient fortification – a form of supplementation – to prevent iodine, folate, niacin, and thiamin deficiencies. So at least one branch of the government is convinced some supplementation is desirable.

The Iowa Women’s Health Study

The study followed a large number of women in Iowa, and queried them several times about supplement use. In 1986, the baseline, the women had an average age of 62 (range of 55 to 69) and 66% were taking supplements. By 2004, the surviving women had an average age of 82 and 85% were taking supplements.

Here is the data on overall mortality vs supplement use:

“Cases” are instances of someone dying. “HR” or hazard ratio is the likelihood of dying if you supplement divided by the likelihood of dying if you don’t. Note that all the hazard ratio estimates are “adjusted.”

We can calculate the raw data from the Users and Nonusers columns. In general, supplements had no obvious effect – certainly no statistically significant effect. The fraction of Users and Nonusers who died was essentially identical. If we eliminate copper which only had 229 supplementers, the hazard ratio of supplementers averaged 99.8% that of non-supplementers – i.e., supplementers were very slightly less likely to die.

But – and this is a key point – supplement use increased with age throughout the study. Roughly, 66% of 62 year olds took supplements and 82% of 82 year olds took supplements. But mortality at age 82 is about five times higher than mortality at age 62. So the high-mortality 82 year olds were supplementing more than the low-mortality 62 year olds, but supplementers had the same mortality as non-supplementers! This indicates that with age adjustment, supplementation would have shown a clear benefit.

Did Mursu et al offer an age-adjusted analysis? No, they did not. The next column in the table is age-and-energy-adjusted. “Energy” means calories of daily food intake. But the purpose of eating is to supply our body with nutrients, and supplementing nutrients reduces appetite and energy intake. (This is discussed in Chapter 17 of our book.) Lower energy intake is associated with better health, largely because a high proportion of the elderly are diabetic: 27% of those over age 65 or older are diabetic, and 50% are diabetic or prediabetic; diabetics and prediabetics benefit from lower energy intake. By adjusting for energy, they are removing credit from the supplements for the health improvements due to reduced energy intake.

Nevertheless, after age-and-energy adjustment, we find that supplements generally decreased mortality. Nine of the fifteen supplements decreased mortality, five increased mortality. At the 95% confidence interval, five supplements decreased mortality, only one increased mortality.

Making the Elephant Wiggle His Trunk

With four parameters I can fit an elephant, and with five I can make him wiggle his trunk.

Mursu et al used multivariable adjustments with 11 parameters and 16 parameters respectively to obtain their “results.” Using so many parameters lets the investigators generate whatever results they want.

I don’t think it’s a coincidence that both multivariable adjustments substantially increased the hazard ratio of every single one of the 15 supplements. The 11-variable adjustment increased hazard ratios by an average of 7%, the 16-variable adjustment by an average of 8.2%.

Rest assured, it would have been easy enough to find multivariable adjustments that would have decreased hazard ratios for every single one of the 15 supplements by 7 or 8 percent.

I believe it verged on the unethical that the variables chosen include dangerous health conditions: diabetes, high blood pressure, and obesity. These three health conditions just happen to be conditions that are improved by supplementation.

Anyone familiar with how regression analyses work will immediately recognize the problem. The adjustment variables serve as competing explanations for changes in mortality. If supplementation decreases diabetes, high blood pressure, and obesity, and through these changes decreases mortality, the supplements will not get credit for the mortality reduction; rather the decreased diabetes, blood pressure, and obesity will get the credit.

It’s appropriate to ask: if it’s proper to include health conditions like diabetes as variables in the regression, why not include other health conditions like cancer? The likely answer: Supplementation does not generally help conditions such as cancer, so including such conditions as adjustment factors would not have made the supplements seem more harmful. Rather, by giving greater weight to diabetes and obesity – conditions supplementation benefits – it would have made supplements look more beneficial.

It is impossible to take seriously studies that provide 11- and 16-variable adjustments, with arbitrarily chosen adjustment factors and no sensitivity analysis showing how alternative choices of adjustment factors would have altered the results.

Conclusion

The great economist Ronald Coase (in his essay “How should economists choose?”) said, “If you torture the data enough, nature will always confess.”

The Mursu paper was an exercise in torturing data until it declared, “Supplements are harmful!”

The Offit piece is a polemical exercise pretending that an unsettled part of biology – our nutrient needs, and the circumstances in which food fails to meet them – is a settled subject with a simple answer.

Now, it’s quite difficult to establish the healthfulness of supplementation in general, because you can always get too much of a nutrient, nutrient needs differ among persons depending on their health and age, and whether a person will benefit from a nutrient depends on whether the rest of the diet is deficient in that nutrient. So any given supplement is going to be harmful in some circumstances, beneficial in others.

A proper scientific approach would be to try to determine the circumstances under which supplements (or dietary changes eliminating the deficiency) would be beneficial.

51 Comments.

I think it’s very telling that the only supplement strongly associated with mortality is copper.
Copper is a very specific nutrient to supplement, and its use almost always indicates rheumatoid arthritis.
It always stands out in this kind of study, but that may say more about arthritis than copper.http://www.ncbi.nlm.nih.gov/pubmed/1578095

Follow the diet, bought the book and have been a long-time lurker. I hope this isn’t too far OT, but some of us are very familiar with Paul Offit and I was surprised to see him mentioned here. My son suffered a very serious pediatric vaccine reaction four years ago of which he is now finally recovered. Vaccine safety is personal to us and other parents that have also experienced similar reactions. Offit has a history with us.

That he penned a dishonest screed pushing his pet narrative in no surprise; he’s been doing so for years. Check out this correction the Orange County Register printed regarding an Offit interview where he made multiple untrue, disparaging accusations against CBS reporter Sheryl Attkisson (of Fast and Furious and Benghazi fame) after she reported on his pharma conflicts of interest.

You also described Offit as “best known for his defense of childhood immunizations”. While that is true, you didn’t mention that Offit is a patent holder for Merck’s Rotateq pediatric vaccine. He won’t say how much he made, but it is estimated his royalties resulted in millions. He has a vested financial interest in high childhood vaccine uptake rates. Mark Blaxill exposed this guy long ago.

I think excessive glibness that enables one to rationalize premature conclusions, especially lucrative conclusions, is a major problem. His vitamin piece is a good example. It doesn’t make me optimistic that his other work is sound.

Really interesting post – this is what I love about your blog (and your book), not just that you can disagree strongly and convincingly, but that you can do it politely and without resorting to polemic in the place of actual arguments. Bravo.

I’ve always been a get-it-from-food kind of person, but I recently started tracking my nutrient intake and realized that despite a extremely high vegetable consumption I’m still falling short of your Vitamin C recommendations, and you make such a good case for them that I think I may have been persuaded to start a supplement.

I may be offbase here, but would it be fair to attribute the popularization of mega dosing to Pauling? That’s what I’ve always associated him with, esp with vit c. The medical community had recognized it as a cure for scurvy, but didn’t support the massive dosing he recommended for misc symptoms in healthy people. And then, of course, they were so convinced they were right they refused to test it. Very strange way to do science. But anyway, supplementation for a healthy person to achieve “extra” health is a slightly different question than supplementation in a case of deficiency or extra requirement, but they do seem to get wrapped all in together, don’t they?

Doesn’t it depend on what the definition of “mega-dosing” is? Many mammals naturally produce mega-doses of Vitamin C internally that makes the current RDA look like a pimple on the ass of an elephant. At what point does Pauling’s “mega-dosing” with respect to Vitamin C extend to other vitamins? Is a B-Complex at 50mg or 100mg “mega-dosing” despite therapeutic efficacy?

Yes, it’s the therapeutic levels that need to be figured out for all of of the vitamins, and I think Dr. Jaminet’s work, because it recognizes the toxic levels as well as the benefits, is really fantastic. Because often these things are recommended without any real understanding of caution. Usually it is presented as “more is better”. Essential omega 6, for example, is sold as a supplement, and is used to sell sunflower seed oil as well, and probably we should not supplement it at all. I associate this type of reckless vitamin supplementation as beginning with Pauling. I may be wrong on that, though, that’s why I was asking. In all fairness to him, of course, is that vit C does seem to have a very low toxicity even at the high doses. And also, it took a long time to determine the toxic doses of anything as no one would study it.

I’ve read about the high level of Vit C that some authors recommends based on the levels that mammals can produce internally. It seems to me however, that we have lost the ability to produce Vitamin C so far back in our evolution that we must have some degree of adaption to lower levels.

I agree with you, Paul: any time I see “adjusted” data, I become somewhat suspicious…doubly so if the unadjusted data is not reported, or if the specific adjustments are not disclosed. Even with full disclosure, it’s far too easy to test out different combinations until the adjustments produce the correlation you want.

Of course, once we discount all the studies which consist entirely of mining the Nurses’ Health Study and the Health Professionals Followup Study datasets in order to fabricate associations by which to justify existing nutrition policy, there’s not much left holding it up!

Paul, great post, glad to see your cranking them out again.
Paulings recommendations on vitamin c supplementation was based upon research that showed that animals manufacture on average 5,400mg of vitamin C daily and considerably more when under stress or ill. Why do you believe Paulings inference is mistaken?

Completely off topic. I did my own research and lost about 60 lbs and felt much healthier and happier. I was semi seriously thinking about writing a book until I found your website and book, and discovered you had already written the book I would have liked to write. Now, when anyone asks about my weight loss, I refer them to your website. However, there are a couple of things that are still bothering me that I can’t seem to find much research on:
1. I agree that white rice seems to be the one grain that has successfully supported multiple cultures without disease, but why are these cultures generally short? Before you say genetics, within several generations of moving away from rice, the decedents are much taller.
2. You have touched on essential amino acids in various posts, but this seems to be a very underserved aspect of nutrition. What studies and recommendations ARE out there seem to conflict in regards to total amounts and ratios of essential amino acids. One interesting source of information is those studies done on swine feed. I would have expected them to be in much closer agreement to those done on humans… but this doesn’t appear to be the case. I started supplementing with Lysine recently to combat herpes… and it seems to have been the missing piece of continued fat loss and muscle gain. I would be interested in your thoughts.

Hi Paul,
Interesting post! A couple comments about the Mursu paper. I think you are right about the possibility that the real effect of supplements is being masked by the other covariates. Depending on the details of model optimization, the “explanatory power” dumped into one variable or another could be difficult to parse. If your specific alternative hypotheses are correct, however, I would expect a high covariance between the supplement covariates and energy-intake or diabetes-presence/absence.

Being a typical cookie-cutter epi paper, however, the full details of their models are not available even as appendices, let alone the raw data. Therefore, it’s not easy to check whether this is so. Although every field develops its own rules of thumb, I would personally feel more comfortable with this sort of thing if details/rationale of model selection were given.

On a side-note, I’ve never understood why they wouldn’t just use generalized linear models, for which model selection and hypothesis testing would be straightforward. Also, Bayesian methods would allow us to incorporate realistic prior information about the effect of conditions like diabetes on hazard rates.

Thanks for this Paul. I’ve got stubborn older parents with various and sundry health problems, and I keep trying to convince them to take supplements and read your book and site. I bought copper, zinc, vitamin D3, magnesium, iodine and K2 via your site for them to start, but they refused, citing that they don’t like the idea of popping multiple pills and it’s too time-consuming/troublesome.

Failing that, I’m asking them to take a multivitamin 2-3 times per week but even so, they are stubborn.

My mother insists that taking supplements beyond what you get in food places unnecessary harm on your kidneys. She has continual angular cheilitis and also was diagnosed with osteopenia. She spoke with her doctor about Vitamin K2 and the doctor told her there was no proof for its aid and that the studies were inconclusive and told my mother to keep taking her calcium and Vitamin D supplement.

My mother also believes that if the vitamin/mineral were truly necessary, the FDA would add it to food like D in milk and iodine in salt. Her cholesterol also tested below 100 and she often has tooth problems.

My father is receptive to some PHD facts, especially as a cancer survivor, he is convinced that starting a lot of supplements at once will confound his symptoms (a slight swelling/pain in his upper right abdomen and an ultrasound and complete metabolic profile found nothing extraordinary; fatigue; and hypochloridia which has changed the lining of his nails and clearly affected his ability to absorb minerals from his food; and fasting blood sugar greater than 100) and he won’t be able to isolate the effect of each supplement or the supplements will make his lab results wonky. He also trusts his doctors absolutely and eats shredded wheat for breakfast every morning.

Nevertheless, they believe they are in fairly good health regardless of these health issues at what I still consider spring chicken ages of 58 and 57, because they are not obese.

It’s heartening to read this and have you as a resource, but if only nutrition and medicine could make up, and catch up doctors and medical guidelines! If only your book were required reading in medical school curriculums!

Keep fighting the good fight and know that you’ve got us on your side. Thanks for all you and Shou-Ching have done and continue to do.

Sorry if my question is a bit off-topic for this post, but I didn’t know where else to fit it in, thanks in advance!

As a weight lifter, I want to incorporate the tenants of the PHD, but I also see value in post workout meals consisting of high protein/high carbs/low fats. I’m following the PHD most days, but 2-3 times a week after heavy lifting, my largest meal of the day, a post workout dinner consisting of lean meats (chicken breasts/lean beef/etc.) and carbs(white rice, potatoes) with little to no fats. This spikes insulin and helps in building muscle while fat intake is minimal so that adipose tissue does not grow.

This works great for muscle growth, but my concern is whether it will cause my blood glucose to fluctuate into abnormal levels the rest of the time, whereas they stay consistently in a healthy range when I’m strictly PHD.

Any thoughts on doing the PHD for someone who wants to maintain significant lean muscle mass while remaining in lower bf% ranges?

As I recall, there’s a 2-3 hour window after working out where the muscles are glucose sensitive, so no metabolic damage is done if you keep the excess carbs to that window. A solid food meal takes a long time to be absorbed though, so you would be better off ingesting a pre-workout drink instead. I think Paul recommended 25g of carb per hour which is lower than the traditional recommendation (.8g/kg). So 25g dextrose plus enough BCAA, leucine or hydrolized whey/caseine to stimulate muscle synthesis (>3g leucine). Drink 45mins to an hour before working out.

If I were you I would try to combine Leangains style intermittent fasting with overall PHD eating. The leangains intermittent fasting is very compatible with PHD intermittent fasting. Check it out at leangains-guide.

That is what I am doing, though I came around to this by self experimentation and PHD rather than following Leangains. I was off put by his writing, but I think he stumbled onto something legitimate. I lift a lot, and basically my day looks like this: Breakfast is coconut oil and 6 grams of Lysine to promote ketosis/simulate fasting but still taking in some calories. Thirty minutes before working out, I take 16 grams of BCAA’s. I work out around noon, and have my largest (and sometimes only meal) within a hour of working out. I eat all of my carbs during this time. Later, if I am hungry, I will eat some fat and protein. I have lost 70 lbs and am still the same strength this way without “dieting” (aka hunger).

I wish I could edit my posts. One thing that I found interesting about Leangains is even though he recommends BCAA’s, he is actually taking a more balanced mix of EAA’s. After reading PHD, I am not sure the EAA mix he uses is optimal, but it may be better than the normal BCAA mixes. Hence the Lysine. I am also thinking about adding Threonine. The EAA mix used by Leangains includes methionine and histidine which are potentially problematic.

Have you been measuring your blood glucose levels at all? I’m currently switching from pure PHD to leangains. I’m fasting 16 hours every day, for lunch I eat 3 eggs and veggies with coconut oil every day, on lifting days I eat lean meats and potatoes for dinner pwo above maintenance calories, on rest days my dinner is fatty meats/seafood and low-carb veggies with coconut oil below maintenance calories.

I’m pretty sure this will be great for physique and general health, but I fear that the heavy carb and protein meals without fats on lift days will spike insulin and throw off my bg.

I have not. Other than making sure I am doing the restricted feeding windows and when I do eat, it is within the guild lines of PHS, I have been trying to listen to what my body wants. I have continued to get stronger and leaner. If this stops, I may reassess and try to be more specific on what I eat and how that effects my blood glucose levels. But I am not convinced that a spike in insulin is bad, especially post work out, as long as total insulin levels for a given time period are low. In healthy people, an insulin spike can actually result in lower insulin levels over time. This is actually one of the criticisms of the zero carb diets. (That no glucose/insulin spike eventually results in a constant elevated level of insulin.) Now, if you are a diabetic, all bets are off. By the way, I have changed my supplements slightly and have been having better results. I take all the EAA right before working out now instead of having some with the morning coffee. I take 3 g of Isoleucine, 9 g of Leucine, 8 of Lysine, 4 of Threonine, and 3 of Valine. I am continuing to experiment and so far this is the best mix. I was taking a mix low in Isoleucine and Valine and that turned out to be no fun at all.

A couple of anecdotes for the discussion: I know two women who have taken multivitamins for many, many years. One was actually taking one in the morning and one at night. She’s in her early 90s now, and last I knew she was still climbing the stairs to the balcony in her church on Sundays and playing the organ like the pro that she is. The other woman only took one a day. She’s pushing 102 and still living in her own apartment in an assisted living facility, cooking two of her own meals a day. I don’t think either of them used supplements beyond the multivitamins.

Your post reminds me of the unique balance of the body! How wondefully designed it is. Have you heard about “live blood analysis”? What is your take on it to find or shed light on problems? Despite eating PHD and a doctor’s care, my chronic inflammation and chronic immune stress markers, T3 levels, cholesterol levels, anemia have only gotten worse. Multiple labs do not show the answers–a doctor suggested “live blood analysis” to shed light. Is this a viable technique?

or what do you think about “nutrition response testing” or muscle-respose testing based on electric energy, muscle response, neurology, reflexes?

well, after being on PHD for a little over a year, and experiencing some improvement in symptoms, but not all, I got some Metametrix ecology profile results back. I have 2 parasites, taxonomy unidentifiable, and some detected fungal overgrowth.

Does anyone here have experience with anti-protozoal drugs such as Nitazonxanide?

I’ve read on sites such as badbugs.org that stronger antibiotics may be required. Any experience or thoughts would be welcome.

Forgot to mention that I also have high levels of opportunistic bacteria, Achromobacter/Alcaligenes. They are equivalent in number to or greater than the numbers of typical predominant bacteria in my gut. I think this is a result of being prescribed iron pills for too long two years ago. Changing your gut takes a long time!

I think there are some instances where the body has accumulated an excess of one nutrient due to a lack of another. Examples include excessive copper accumulation due to lack of zinc; fluoride (in the thyroid) due to lack of iodine, and excessive sodium in the cells due to lack of potassium.

So I think we need to take into account that we´re living in a world where some minerals are found in higher than natural concentrations. People didn´t use copper pipes in the stone age, copper sulfate wasn´t added to water to control algae etc. They didn´t use fluor toothpaste, they didn´t get much salt, and certainly not pure NaCl, they almost allways had very high intakes of potassium.

They also didn´t obtain all that much copper from the diet, which is mainly found in grains, seeds and nuts, and they didn´t get all this phytic acid that can bind to zinc and prevent its absorption.

Analysis now suggest some people have almost as much sodium as potassium in their bodies, whereas wild animals, hunter gatherers etc would have many times more potassium than sodium, even saltwater fish have more potassium:sodium than most humans in the developed world (Asian countries being an exception). I think we should consider salt a toxic metal if consumed in excess, just like any other. Why should we expect our cells to work optimally with all this accumulated sodium. Should cancer and diabetes surprise us?

Indeed people that have done longer water or juice fasts can experience horrible effects from breaking this fast with lots of sodium, suggesting that the body is not designed for too much of this mineral (esp. in relation to potassium).

As for zinc, I think the suggestion of adding 50 mg of zinc once per week on the supplement section may be a bit misleading. First of all, it is fairly common to have zinc deficiency, but very uncommon to have zinc toxicity. For copper it is opposite. Yet there´s the recommendation of 2 mg copper per day. Then there´s the problem that some forms of zinc are poorly absorbed/utilized by the body, like zinc gluconate, oxide, whereas zinc orotate is very well utilized. There´s also a big gender difference as males need lots of zinc for semen production. It has been suggested that 5 mg dietary zinc is needed to make up for what is lost in one ejaculation. Some men supplement 50 mg zinc daily (not weekly!) to improve sperm quality. I suspect in the future various health problems and ailments in relation to low zinc will be better known, for example enlargement of the prostate (affecting almost 50% of males in their fifties) could be largely due to a zinc deficiency. Infections and digestive disorders, allergies… ailments that many people here seem to suffer from can likely be greatly helped with proper zinc supplementation. Zinc supplementation could be an easier and more sensible approach than low carb, high vitamin C, lauric acid, probiotics, antimicrobial herbs, food elimination, whatever… Those that suffer from leaky gut could experience it to be healed dramatically faster with adequate zinc.

There´s also the fact that zinc content in the human body is more than 30 times higher than for copper. And magnesium is «only» like 8 times higher than for zinc. Yet there´s recommendation here of 200 mg supplemented magnesium (1/8 of that is 25 mg), and 2 mg copper (30x that is 60 mg).

They have some things that you don’t suggest supplementing, but almost all of the things that you do suggest. I have no connection with the company, I’m just wondering what you think. The idea of swallowing one pill vs. a fistful is tempting when you’re tummy is sensitive.

Hi Paul-
What is your opinion of supplementing with unmodified potato starch? It appears to be gaining in popularity in the paleosphere with reports of improved digestion, bio-markers and other gains in health. Thanks.

Paul, I’m really surprised and disappointed that you failed to point out WHY folic acid isn’t a good idea — because it’s synthetic and blocks the active forms of folate (like folinic and methylfolate).

I’m on disability so unable to afford your book. I did find a portion of it doing a google search, and all I could see was a discussion of the negative aspects of folic acid fortification and a suggestion that choline helps improve folate status.

I know I should be eating more choline rich foods, especially eggs, but every single time I try, I get palpitations. Would lecithin be a way to perhaps try slowly increasing choline and then transitioning to egg yolk?

I’ve had weird reactions to choline supps in the past (elevated acetylcholine levels) but found a couple of studies that suggested both b12 and carnitine deficiencies can result in low acetycholinesterase levels.

I’ve been supplementing with both, so hopefully I’ll be able to tolerate the lecithin and/or choline.

Mainly significantly increased muscle twitching and cramping, but also increased anxiety and irritability.

There were times when I was also eating potatoes, and I think doing so made these symptoms even worse. Following up a few months later, I found this paper which talks about solanine blocking acetycholinesterase:

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